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Abstract

The cobalt-catalysed alkylative aldol cyclisations of α,β-unsaturated amides with an
appendant ketone were studied using a range of trialkylaluminium reagents.
Investigations revealed that Co(acac)2·2H2O acts as an effective precatalyst for this
transformation and the reaction provides β-hydroxylactam products containing three
contiguous stereocentres with high levels of diastereoselection. The substrate scope
of the reaction was explored and attempts were made to develop an asymmetric
variant of this process. Two plausible reaction mechanisms have been proposed; the
first invokes a π-allylcobalt species as a key intermediate in the reaction mechanism
and the second involves a radical-mediated pathway. A stereochemical rationale for
the observed relative stereochemistry of the β-hydroxylactam products has been
discussed.
II. Rhodium-Catalysed Carbometallations of Ynamides in the Preparation of
Multisubstituted Enamides
A highly stereo- and regioselective rhodium-catalysed carbozincation of ynamides
using organozinc reagents has been disclosed. A careful examination of ligand
effects on the rhodium catalyst yielded a complementary set of hydrozincation
conditions. The alkenylzinc intermediates produced during the course of these
reactions have been harnessed in further transformations with electrophilic species
and in cross-couplings, thus providing access to multisubstituted enamides in a
stereo- and regioselective fashion. Additionally, a rhodium-catalysed tandem
carbometallation−conjugate addition with ortho-boronate substituted cinnamic acid
derivatives has been described. The enamide−indene products were obtained in good
yields and regioselectivities. Preliminary work has been undertaken on an
asymmetric variant of this transformation and the initial results have been reported.